This is an extensively revised application for funds to support a longstanding neuropathology training program based on molecular research in disease-based neuroscience. This program emanates from an institution renowned for the integration of cellular and molecular technologies to the study of neurologic disease. This tradition will be continued by a vibrant, multidisciplinary training faculty committed to offer a comprehensive and integrated "Neuroscience Experience" and to further enforce a scientific environment that is highly conducive for research training. The program is run by an 18 member, highly interactive training faculty with independent research funding and a long history of collaboration. The main goal of the program is to support the training of predoctoral (2 requested) and postdoctoral fellows (4 requested) with state-of the-art molecular approaches to disease-based neuroscience. The Program embraces colleagues in the Depts. of Pathology, Neuroscience, Developmental Molecular Biology, Cell Biology, Microbiology and Immunology and Genetics, and has been instrumental in allowing the involved faculty to maintain prominence in a number of disease entities. We retain a strong presence in Alzheimer's disease and Multiple Sclerosis research, Neuro- AIDS research and Lysosomal Storage Diseases. Parkinson's and Huntington's Diseases were recently included in the list of degenerative disorders researched by newly recruited faculty. Trainees will use cutting-edge molecular, proteomic, structural, genetic and clinical approaches to investigate questions of fundamental importance to neurological diseases including neuroinflammation, neurodegeneration, neuronal and glial cell lineages, development and functions. During the past funding period, we have been very successful in fulfilling an important mandate of a training program, which is to guide trainees to develop into independent scientists. Altogether, the majority of our trainees (around 90%) are still active in neuroscience research and 48% of our former post-doctoral trainees (2000-2010), now hold a faculty appointment. This renewal NRSA, with its 30+ year history, continues to be the major source for pre- and postdoctoral trainees in research in the mechanisms of neurologic disease at this institution and continues to attract first-rate, productive scientists who remain in science after training.